Objective. Congenital adrenal hyperplasia (CAH) shows a range of severity which is explained in part by the different mutations of the CYP21 gene. To better understand the incomplete concordance between genotype and phenotype in CAH the role of the sensitizing N363S polymorphism of the glucocorticoid receptor (GR) was examined in CAH patients.

Design. CAH patients were screened for N363S. Laboratory findings and clinical characteristics of carriers and non-carriers were analyzed retrospectively.

Methods. The CYP21 gene of two hundred CAH patients was analyzed by allele specific PCR. The GR gene was tested for N363S by PCR followed by RFLP. Antropometric data (height, weight), degree of intrauterine virilization, hormone concentrations (17-OH-progesterone, DHEA, aldosterone, testosterone, plasma renin activity), substitution doses and clinical course were analyzed.

Results. The carrier frequency of N363S in CAH patients was equivalent to that of the general Hungarian population (6% vs. 7.8%). Interestingly, none of the non-classical CAH (NC-CAH) patients were carriers of the polymorphism. Carrier girls had milder genital virilization than mutation-matched non-carrier controls. There was no significant difference regarding the substitution doses, neither hormonal, nor the auxiological parameters.

Conclusions. The association of sensitizing GR variant with the impaired cortisol production in CAH might be compensatory in mild NC-CAH and may prevent severe intrauterine virilization in classical form. Although the exact role of N363S in the extrauterine life should be further investigated, the consideration of certain genetic polymorphisms of CAH patients may lead to better, individualized therapeutic regimens.

Dóra Török MD, PhD

Semmelweis University, Faculty of Medicine, 2nd Dept. of Paediatrics,
Budapest, Tűzoltó u. 7-9, H-1097, Hungary
E-mail: torokdora@yahoo.com
Fax:+36-1-217-57-70